Background and Importance Within the post-operative period following a solid organ transplantation, multidisciplinary teams prioritise tacrolimus administration per os to minimise the neurotoxicity associated with its use via continuous intravenous infusion. Despite being classified as a hazardous drug, there is no tacrolimus liquid dosage form commercially available ready for direct administration by oral route.
Aim and Objectives To validate physical, chemical and microbiological stability of an affordable extemporaneous tacrolimus oral solution/suspension in single-dose disposable polypropylene syringe.
Material and Methods A search on chemical compatibility between tacrolimus and polypropylene was accomplished. The formulation developed for study case was split in three samples stored at 20–25°C and three others at 2–8°C, ensuring every assay was performed in triplicate.
Stability parameters were tested every 7 days for a 28-day period. The analysis included organoleptic properties, sedimentation time, homogeneity, pH, redispersibility, crystal growth and weight variation. In order to identify and quantify any potential colony-forming unit (CFU), cultures with blood agar were read after 24 and 48 hours from incubation at 37°C, whereas Sabouraud agar cultures were read after 24, 48, 72 and 96 h.
Results Chemical stability of tacrolimus 1 mg/mL suspension formulated with 1:1 Ora Plus® and Ora Sweet® in polypropylene syringe was reported.
For the present study, tacrolimus 1 mg/mL suspension based on a 2:1 blend of simple syrup and carboxymethylcellulose 1.5% aqueous gel was developed since its composition is simpler and saves €8,51/100 mL.
Physical and chemical parameters remained constant during all the study period regardless of storage temperature: The formulation was homogeneous, sheer with yellowish hue and sweet. No crystal growth or sediment were observed. Median weight variation was 0.96% for the fraction stored at 20–25°C (0.38%–1.65%) and 0.75% for the stored at 2–8°C (0.58%–1.08%). Average pH values were 5.70 (5.60–5.76) and 5.72 (5.70–5.76) respectively.
One Staphylococcus hominisCFU was detected on day 14 in one sample stored at 2–8°C. No subsequent microbial growth was found, therefore it was considered contamination
Conclusion and Relevance Tacrolimus 1 mg/mL oral suspension in simple syrup and carboxymethylcellulose 1.5% in a 2:1 ratio is stable when conditioned in polyproplylene syringe for 28 days and stored at room or refrigerator temperature.
Conflict of Interest No conflict of interest
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